The overall aim of this research is to investigate a spontaneously occurring model of airway obstruction and bronchial hyperreactivity, two features of human asthma. Horses and ponies with chronic airway disease develop acute exacerbations of disease when housed in a barn. These exacerbations result in airway obstruction, airway hyperreactivity and altered autonomic regulation of airways, some of which persist during periods of clinical remission. The aims of this proposal are to investigate autonomic regulation of airways in more detail and to determine the role of airway epithelium in autonomic responses in diseased (principal) and healthy (control) animals. A combination of in vivo and in vitro techniques will be used. In anesthetized animals we will determine the distribution of the parasympathetic, sympathetic and nonadrenergic inhibitory nervous systems. Electrical stimulation of the vagus nerve and administration of a ganglion-stimulating drug will be used to activate the autonomic nervous system in adrenal intact and adrenalectomized animals. Mechanical properties of lungs will be measured and specific receptor blocking agents will be used to define autonomic responses. Our principal aims are to determine if horse and pony airway smooth muscle receive sympathetic innervation and possesses a nonadrenergic inhibitory nervous system which becomes altered in disease. Isolated strips of trachealis muscle, bronchial rings and lung parenchymal strips will be studied in vitro. Tissue preparations will be mounted in organ baths and contractile responses studied. Field electrical stimulation, and specific autonomic agonists and antagonists, will be used to determine the responses of smooth muscle at different levels of the tracheobronchial tree to autonomic stimulation Control and principal ponies will be studied, the latter group being studied both in clinical remission and with airway obstruction. Removal of epithelium from trachealis and bronchial ring preparations and use of the epithelial sandwich technique will demonstrate the importance of epithelium in autonomic responses. Finally, radioligand binding ans autoradiography will define the number and activity of adrenergic receptors at different points in the tracheobronchial tree of control and principal animals.